Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children

Abstract

Background: Where P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas.

Methodology/principal findings: A cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season.

Conclusions/significance: Under high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2(nd) and 3(rd) year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections.

Figure 1. Schematic map of study area including participants' house (dots), health centres (crosses), roads (black lines) and rivers/streams (blue lines).

Figure 2. Prevalence of malaria at regular cross-sectional surveys: A) first samples only, B) double bleed samples 24 hrs apart, C) study retention profile.

Figure 3. Incidence of P. falciparum and P. vivax clinical episodes with different parasitaemia threshold for individual 8/9 weekly intervals.

Figure 4. Age dependence of risk of malarial infections: age-prevalence at 7 cross-sectional survey time points with 2 consecutive bleeds 24 hrs apart.

GEE model based estimates and semi-robust standard errors for age categories. Fitted lines: best fitting 1^st, 2^nd or 3^rd degree polynomials of age as continuous variable.

Figure 5. Age dependence of risk of malarial illness: Effect of age at start of 8/9 weeks follow-up period on incidence of malarial illness with different parasite cut-offs.

GEE model based estimates and semi-robust standard errors for age categories. Fitted lines: best fitting 1^st, 2^nd or 3^rd degree polynomials of age as continuous variable.

Figure 6. Association of personal bed net use on risk of malarial infections and disease.

Closes circles: univariate estimates, open triangle: adjusted for age and time trends, closed diamonds: age, time and village adjusted, open squares: estimates from best fitting model (see Table 1 & 2). All estimates from GEE model with semi-robust standard errors.